Trial of Aeroquin Versus Tobramycin Inhalation Solution (TIS) in Cystic Fibrosis (CF) Patients

Phase 3

Completed

Conditions: Cystic Fibrosis

Interventions: Drug: TIS (Tobramycin Inhalation Solution)
Drug: MP-376 (Levofloxacin Solution for Inhalation)

Registration Number: NCT01270347

Lead Sponsor: Amgen

Brief Summary: Patients with cystic fibrosis (CF) suffer from chronic infections of the lower respiratory tract that can be caused by one or multiple bacteria, including Pseudomonas aeruginosa, which has been particularly problematic to eradicate and been implicated as the major cause of morbidity and mortality in CF patients. Aerosol delivery of antibiotics directly to the lung increases the local concentrations of antibiotic at the site of infection resulting in improved antimicrobial effects compared to systemic administration. Bacterial resistance to current aerosol antibiotic treatments indicate a need for improved therapies to treat CF patients with pulmonary infections caused by multi-drug resistant Pseudomonas aeruginosa and other bacteria. High concentrations of MP-376 delivered directly to the lung are projected to have antimicrobial effects on even the most resistant organisms.

Detailed Description: This study will assess the comparative safety of MP-376 (Aeroquin) and Tobramycin Inhalation solution (TIS) \[TOBI® Novartis Pharmaceuticals\] over three consecutive cycles of 28-days treatment followed by 28-days off in stable CF patients with chronic P. aeruginosa lung infection. Efficacy data for MP-376 and TIS at the end of the first 28-day treatment period will also be compared, as well as explored over multiple treatment cycles.

Study patients participating in Mpex 209 will be given the option to participate in a six-month open label extension phase of the Mpex 209 protocol. The open label extension will allow enrolled patients to receive three additional courses of MP-376 (levofloxacin inhalation solution, Aeroquin™).

Study with completed results acquired from Horizon in 2024.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 282

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
TIS	TIS (Tobramycin Inhalation Solution)	Tobramycin Inhalation solution (TIS) \[TOBI® Novartis Pharmaceuticals\]
Aeroquin	MP-376 (Levofloxacin Solution for Inhalation)	Aeroquin, Inhaled Levofloxacin (MP-376)

Primary Outcome Measures

Name	Time	Method
Number of Participants With Treatment Emergent Adverse Events (TEAEs)	From start of study until end of the study (up to 168 days)	An AE was defined as any unfavorable or unintended sign, symptom, or disease temporally associated with the use of a Study Drug, whether or not considered related to the Study Drug. An AE could potentially be a new disease, any untoward event, or an exacerbation of a pre-existing condition. AEs included, but were not limited to: Any symptom not previously reported by the patient (medical history) An exacerbation of a pre-existing illness An increase in frequency or intensity of a pre-existing episodic event or condition A condition first detected or diagnosed after Study Drug administration even though the condition may have been present before the start of the study Overdose of Study Drug
Relative Change From Baseline in Percent Predicted Forced Expiratory Volume in One Second (FEV1)	Baseline, day 28	FEV1 was the volume of air exhaled in first second of a forced expiration as measured by spirometer. Least squares (LS) mean and standard error (SE) were determined from an analysis of covariance model with terms for treatment, region (US, non-US), and age (12 to 18 years, \> 18 years), and Baseline FEV1 (\< 55%, . 55%).

Secondary Outcome Measures

Name	Time	Method
Number of Participants in Each Category of Percent Change From Baseline in FEV1	Day 28	FEV1 was the volume of air exhaled in first second of a forced expiration as measured by spirometer.
Percent Change From Baseline in Forced Vital Capacity (FVC)	Baseline, day 28	LSMean and SE were determined from an ANCOVA model with terms for treatment, region (US, non-US), age (12-18 years, \>18 years), baseline FEV1 (\<55%, \>=55%), and baseline as a covariate
Percent Change From Baseline in Average Expired Flow Over the Middle Half of The FVC Maneuver (FEF25-75)	Baseline, day 28	LSMean and SE were determined from an ANCOVA model with terms for treatment, region (US, non-US), age (12-18 years, \>18 years), baseline FEV1 (\<55%, \>=55%), and baseline as a covariate.
Number of Participants in Each Category of Relative Change in Percent Predicted FEV1	Day 28	FEV1 was the volume of air exhaled in first second of a forced expiration as measured by spirometer.
Change From Baseline in Pseudomonas Aeruginosa Sputum Density	Baseline, day 28	Pseudomonas aeruginosa density was measured as log10 colony-forming units \[CFU\] per gram sputum.
Number of Participants in Each Category of Change From Baseline in Pseudomonas Aeruginosa Sputum Density	Baseline, day 28	Pseudomonas aeruginosa density was measured as log10 colony-forming units \[CFU\] per gram sputum.
Change From Baseline in the Respiratory Domain of the Cystic Fibrosis Questionnaire Revised (CFQ-R)	Baseline, day 28	The Cystic Fibrosis Questionnaire (CFQ-R) is a disease-specific instrument that measures health-related quality of life (HRQOL) for adolescents and adults with cystic fibrosis (CF). Respiratory domain assessed respiratory symptoms, score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life.
Number of Participants in Each Category of Change From Baseline in the Respiratory Domain of CFQ-R	Baseline, day 28	The Cystic Fibrosis Questionnaire (CFQ-R) is a disease-specific instrument that measures health-related quality of life (HRQOL) for adolescents and adults with cystic fibrosis (CF). Respiratory domain assessed respiratory symptoms, score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life.

Trial Locations

Locations (34): Childrens Hospital
🇺🇸
Los Angeles, California, United States
Albany Medical College #2
🇺🇸
Albany, New York, United States
Hôpital Pellegrin Enfants - CHU Bordeaux
🇫🇷
Bordeaux, France
Oklahoma CF Center
🇺🇸
Oklahoma City, Oklahoma, United States
CRCM adultes et enfants Service des maladies respiratoires et pédiatrie 1 CHU- Arnaud de Villeneuve
🇫🇷
Montpellier, France
Hôpital Cochin
🇫🇷
Paris, France
CRCM adulte Hôpital Larrey-CHU de Toulouse
🇫🇷
Toulouse, France
Universitätskinderklinik Dresden Mukoviszidose-Ambulanz
🇩🇪
Dresden, Germany
Universitätsklinikum Essen
🇩🇪
Essen, Germany
Schneider Childrens Medical Center of Israel
🇮🇱
Petah Tikva, Israel
Rambam Medical Center
🇮🇱
Haifa, Israel
National Children's Hospital Tallaght
🇮🇪
Dublin, Ireland
Beaumont Hospital
🇮🇪
Dublin, Ireland
Hadassah Medical Center Mount Scopus
🇮🇱
Jerusalem, Israel
Safra Childrens Hospital, Sheba Medical Center
🇮🇱
Ramat Gan, Israel
Cork University Hospital
🇮🇪
Cork, Ireland
St. Vincent's University Hospital
🇮🇪
Dublin, Ireland
Hôpital Necker-Enfants Malades
🇫🇷
Paris, France
Hôpital Haut-Lévêque CHU de Bordeaux
🇫🇷
Pessac, France
Charité Campus Virchow-Klinikum
🇩🇪
Berlin, Germany
Universitätsklinik Gießen und Marburg GmbH Zentrum für Kinderheilkunde und Jugendmedizin
🇩🇪
Gieben, Germany
Ludwig-Maximilians Universität Klinikum Innenstadt
🇩🇪
Munchen, Germany
Dr. von Haunersches Kinderspital der Universität München Christiane Herzog Ambulanz
🇩🇪
Munich, Germany
Katharina-Kasper Kliniken GmbH St. Elisabethen-Krankenhaus Medizinische Klinik
🇩🇪
Frankfurt, Germany
Universitätsklinikum Frankfurt
🇩🇪
Frankfurt, Germany
Universitätsklinikum Kiel
🇩🇪
Kiel, Germany
Kinderärztliche Gemeinschaftspraxis Dr. H. E. Heuer, Dr. C. Runge, W. Sextro
🇩🇪
Hamburg, Germany
Universitätsklinik für Kinder- und Jugendmedizin
🇩🇪
Tubingen, Germany
Birmingham Heartlands Hospital
🇬🇧
Birmingham, United Kingdom
King's College Hospital
🇬🇧
London, United Kingdom
University Hospital Llandough, Penarth
🇬🇧
Penarth, United Kingdom
Belfast City Hospital
🇬🇧
Belfast, United Kingdom
St James's University Hospital
🇬🇧
Leeds, United Kingdom
Castle Hill Hospital
🇬🇧
Cottingham, United Kingdom